Table 2. Clinical studies and case reports on various dietary restriction regimes during cancer treatment.
| First author | Nebeling75 | Safdie152 | Zuccoli153 | Chu-Shore154 | Schmidt155 | Fine76 | Schroeder77 | Champ156 | Rieger157 | Oshakbayev158 | Schwartz159 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Publication year | 1995 | 2009 | 2010 | 2010 | 2011 | 2012 | 2013 | 2014 | 2014 | 2014 | 2015 |
| Number of patients | 2 | 10 | 1 | 5 | 16 | 10 | 11 | 6 | 20 | 1 | 2 |
| Age (years) | P1: 3. P2 (P2): 8.5 | 63 (44–78) | 65 | 8.8 (2.6–47.3) | 50.5 (30–65) | 62 (52–73) | 65 (50–86) | 59.5 (34–62) | 57 (30–72) | 41 | P1: 55. P2: 52 |
| Tumor entity | P1: Stage IV anaplastic astrozytoma. P2: Stage III cerebellar astrozytoma | Various stage IIA–VI carcinomas of the breast (4), prostate (2), ovary (1), uterus (1), lung (1) and esophagus (1) | Glioblastoma multiforme | Tuberous sclerosis complex tumors, among others renal angiomyolipomas and subendymal giant cell tumors | Various stage IV carcinomas and metastases | Stage IV carcinomas of breast (n=2), colorectum (3), lung (2), ovary (1), esophagus (1) and fallopian tube (1) | Stage III and IV head and neck squamous cell carcinoma | Glioblastoma multiforme | Glioblastoma multiforme | Stage III–IV ovarian carcinoma (T3N2M1) | Glioblastoma multiforme |
| Diet type | KD | STS | CR-KD | KD | KD | KD | KD | KD (n=5), CR-KD (1) | KD | CR | CR-KD |
| Energy (kcal/d) | P2: 2 200 | 0 | 600 | NA | NA | 1236±161 | NA | NA | NA | 300–400 | P1: ≈1900. P2: ≈1800 |
| Diet duration | P1: 62 weeks. P2: 8 weeks | 48–140 h before and 5–56 h after CT | 8 months | 40.2 (3–66) months | 7 (0.4–12) weeks | 27.5 (26–28) Tage | 1–4 days | 7.5 (3–12) months | 6–8 weeks or until progress, respectively | 6 months | |
| Concurrent therapy | P1: None. P2: Partly CT | CT | Partly RCT | Sirolismus (1) | None | None | None | RCT (n=4), adjuvant CT (2) | None | Physical activity of at least 10 000 steps per day | None |
| Body weight at diet initiation (kg) | P1: 11. P2: 24 | NA | 58 | NA | 71.5 (46.3–103.4) | NA | 77.8 (64.4–130.2) | 78.3±16.1 | 74 | P1: 85. P2: 79 | |
| Body weight change (kg) | NA | P1 and P2: −3.2 kg. P4: −2.7 kg | −8 (−14%) | NA | −3.0±0.5 (−4.1±0.7%, P=0.08) | NA | −5.7±7.5 (−8.7±7.8%, P=0.05) | −1.86 (−2.2%, P<0,05) | −21 (−28%) | P1: −5(−6%). P2: −5 (−6%) | |
| Early termination due to diet-related side effects | 0 | 0 | 0 | 1 (subjectively perceived cognitive impairment) | 4 (fatigue, familial problems) | 0 | 0 | 0 | 3 (impairment of quality of life) | 0 | |
| Blood glucose (mg/dl) during diet (Change compared to baseline) | P1 and P2: 70–90 | NA | 63 | NA | NA | NA (−3.2±3.7, NS) | NA | 84±7.1 (↓, P=0.02) | 92±9.1 (↓, NS) | 49–95 | P1: <80 (↓). P2: <100 (no change) |
| Ketone bodies (mmol/l) during diet | P1: 4.5–5; P2: 2–3 | NA | NA | NA | P1+P2: 2–4 | ||||||
| Validation of ketosis | Blood+urine | NA | Urine | Blood | Urine | Blood | NA | Urine+blood | Urine | NA | Blood |
| Diet-related side effects | None | P7: Grade I lightheadedness, drop in blood pressure | Mild hyperuricemia, mild hypoproteinemia | NA | None | Grade I constipation (n=2), grade I fatigue (4), grade II fatigue (1) | First 10–15 days: headache, nausea, ichorrhea from the genital tract, skin itching, muddy urine with occasional dysuria and fever up to 38.3 °C | P1: None. P2: Hypercholesterinemia, headache between week 6 and 8 | |||
| Clinical result | P1: 21.77% less FDG uptake after 8 weeks, no change in tumor size on MRI scan, significant improvement in quality of life. Stability until 62 weeks follow-up. P2: 21.84% less FDG uptake after 8 weeks | General and substantial reduction in CT-related side effects compared with ad libitum diet. Low severity of CT-related side effects in four patients who fasted throughout all CT cycles. CT effects on tumor as expected. | After incomplete resection all MRI scans negative until end of diet; relapse 78 days after end of diet | Simultaneous occurrence of tumor growth, stagnation and new tumor formation in 3/3 children; stagnation in 2/2 adults; improvement of epileptic seizures in 3/5 patients | Only 5 of 16 patients able to adhere to diet until study end. These 5 had stable disease. | Significant correlation between stable disease or partial regression in FDG-PET and ketosis relative to baseline | Decrease of mean lactate concentration in tumors | Significantly lower blood glucose levels than in control group, even during glucocorticoid administration | No influence on course of disease | Stable disease | P1: Progress after 4 weeks. P2: Progress after 12 weeks. |
Abbreviations: CR, calorie restriction; CT, chemotherapy; KD, ketogenic diet; NA, not available; NS, non-significant; P1, Patient 1; P2, Patient 2; RCT, radio-chemotherapy; STS, short-term starvation.
We tried to include all studies that gave an indication towards anticancer effects of the intervention.